%0 Journal Article
%T Serum amyloid A triggers the mosodium urate -mediated mature interleukin-1¦Â production from human synovial fibroblasts
%A Kiyoshi Migita
%A Tomohiro Koga
%A Kenshi Satomura
%A Masahiro Izumi
%A Takafumi Torigoshi
%A Yumi Maeda
%A Yasumori Izumi
%A Yuka Jiuchi
%A Taiichiro Miyashita
%A Satoshi Yamasaki
%A Yoshihiro Aiba
%A Atsumasa Komori
%A Minoru Nakamura
%A Satoru Motokawa
%A Atsushi Kawakami
%A Tadashi Nakamura
%A Hiromi Ishibashi
%J Arthritis Research & Therapy
%D 2012
%I BioMed Central
%R 10.1186/ar3849
%X Human synovial fibroblasts were stimulated with MSU in the presence or absence of serum amyloid A (SAA). The cellular supernatants were analyzed by immunoblotting using anti-IL-1¦Â or anti-caspase-1 antibodies. IL-1¦Â or NLRP3 mRNA expressions were analyzed by real-time PCR or reverse transcription-PCR (RT-PCR) method.Neither SAA nor MSU stimulation resulted in IL-1¦Â or interleukin-1¦Á (IL-1¦Á) secretions and pro-IL-1¦Â processing in synovial fibroblasts. However, in SAA-primed synovial fibroblasts, MSU stimulation resulted in the activation of caspase-1 and production of active IL-1¦Â and IL-1¦Á. The effect of SAA on IL-1¦Â induction was impaired in cells by silencing NLRP3 using siRNA or treating with caspase-1 inhibitor. In addition, SAA induced the secretion of cathepsin B and NLRP3 mRNA expression in synovial fibroblasts.Our data demonstrate that exposure of human synovial fibroblasts to SAA promotes MSU-mediated caspase-1 activation and IL-1¦Â secretion in the absence of microbial stimulation. These findings provide insight into the molecular processes underlying the synovial inflammatory condition of gout.Gout is a paradigm for acute sterile inflammation that is triggered by interactions between monosodium urate (MSU) crystals and inflammatory cells in the joint connective tissues [1]. Interleukin-1¦Â (IL-1¦Â) has been identified as a pivotal cytokine in gout and MSU crystal-induced inflammation [2]. IL-1¦Â is induced as an inactive pro-molecule by immune cells, such as macrophages and monocytes, and then cleaved into the active p17 form of IL-1 by caspase-1 [3,4]. Tschopp et al. demonstrated that MSU is capable of activating the NLRP3 inflammasome to process and secrete active IL-1¦Â [5]. These findings suggest that macrophages can recognize MSU as danger-associated molecular patterns (DAMPs) in the damaged tissues and release proinflammatory IL-1¦Â [6]. Upon activation, NLRP3 binds to the ASC, which in turn recruits procaspase-1 for activation. Activated caspase-1 cleave
%U http://arthritis-research.com/content/14/3/R119